7-13932115-G-T

Variant names:

• chr7-13932115-G-T
• rs17136421
• NM_004956.5:c.555-366C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004956.5(ETV1):​c.555-366C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 151,572 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.024 (114 hom., cov: 32)
• Consequence: ETV1 NM_004956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 0 publications found

Genes affected

ETV1 (HGNC:3490): (ETS variant transcription factor 1) This gene encodes a member of the ETS (E twenty-six) family of transcription factors. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. All ETS proteins contain an ETS DNA-binding domain that binds to DNA sequences containing the consensus 5'-CGGA[AT]-3'. The protein encoded by this gene contains a conserved short acidic transactivation domain (TAD) in the N-terminal region, in addition to the ETS DNA-binding domain in the C-terminal region. This gene is involved in chromosomal translocations, which result in multiple fusion proteins including EWS-ETV1 in Ewing sarcoma and at least 10 ETV1 partners (see PMID: 19657377, Table 1) in prostate cancer. In addition to chromosomal rearrangement, this gene is overexpressed in prostate cancer, melanoma and gastrointestinal stromal tumor. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV1	NM_004956.5	MANE Select	c.555-366C>A		intron	N/A	NP_004947.2
	ETV1	NM_001370555.1		c.555-366C>A		intron	N/A	NP_001357484.1
	ETV1	NM_001370556.1		c.507-366C>A		intron	N/A	NP_001357485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV1	ENST00000430479.6	TSL:1 MANE Select	c.555-366C>A		intron	N/A	ENSP00000405327.1
	ETV1	ENST00000405358.8	TSL:5	c.597-366C>A		intron	N/A	ENSP00000384085.4
	ETV1	ENST00000405218.6	TSL:5	c.555-366C>A		intron	N/A	ENSP00000385551.2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3611 AN: 151454 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00876

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00376

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00283

Gnomad OTH AF: 0.0168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0239 AC: 3623 AN: 151572 Hom.: 114 Cov.: 32 AF XY: 0.0228 AC XY: 1690 AN XY: 74056

African (AFR) AF: 0.0779 AC: 3217 AN: 41274

American (AMR) AF: 0.00875 AC: 133 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 23 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00376 AC: 18 AN: 4788

European-Finnish (FIN) AF: 0.000191 AC: 2 AN: 10472

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00281 AC: 191 AN: 67914

Other (OTH) AF: 0.0166 AC: 35 AN: 2110

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.0273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.27
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17136421; hg19: chr7-13971740;